Department of Bioengineering, University of California, Los Angeles, California, USA.
Terasaki Institute for Biomedical Innovation, Los Angeles, California, USA.
Biotechnol Bioeng. 2022 Oct;119(10):2715-2730. doi: 10.1002/bit.28186. Epub 2022 Aug 5.
Microneedles (MNs) have been developed as minimally invasive tools for diagnostic and therapeutic applications. However, in recent years, there has been an increasing interest in developing smart multifunctional MN devices to provide automated and closed-loop systems for body fluid extraction, biosensing, and drug delivery in a stimuli-responsive manner. Although this technology is still in its infancy and far from being translated into the clinic, preclinical trials have shown some promise for the broad applications of multifunctional MN devices. The main challenge facing the fabrication of smart MN patches is the integration of multiple modules, such as drug carriers, highly sensitive biosensors, and data analyzers in one miniaturized MN device. Researchers have shown the feasibility of creating smart MNs by integrating stimuli-responsive biomaterials and advanced microscale technologies, such as microsensors and microfluidic systems, to precisely control the transportation of biofluids and drugs throughout the system. These multifunctional MN devices can be envisioned in two distinct strategies. The first type includes individual drug delivery and biosensing MN units with a microfluidic system and a digital analyzer responsible for fluid transportation and communication between these two modules. The second type relies on smart biomaterials that can function as drug deliverers and biosensors by releasing drugs in a stimuli-responsive manner. These smart biomaterials can undergo structural changes when exposed to external stimuli, such as pH and ionic changes, mimicking the biological systems. Studies have demonstrated a high potential of hydrogel-based MN devices for a wide variety of biomedical applications, such as drug and cell delivery, as well as interstitial fluid extraction. Biodegradable hydrogels have also been advantageous for fabricating multifunctional MNs due to their high loading capacity and biocompatibility with the drug of choice. Here, we first review a set of MN devices that can be employed either for biosensing or delivery of multiple target molecules and compare them to the conventional and more simple systems, which are mainly designed for single-molecule sensing or delivery. Subsequently, we expand our insight into advanced MN systems with multiple competencies, such as body fluid extraction, biosensing, and drug delivery at the point of care. The improvement of biomaterials knowledge and biofabrication techniques will allow us to efficiently tune the next generation of smart MNs and provide a realistic platform for more effective personalized therapeutics.
微针 (MNs) 已被开发为用于诊断和治疗应用的微创工具。然而，近年来，人们越来越感兴趣的是开发智能多功能 MN 设备，以便以刺激响应的方式提供用于体液提取、生物传感和药物输送的自动化和闭环系统。尽管这项技术仍处于起步阶段，远未转化为临床应用，但临床前试验已经显示出多功能 MN 设备的广泛应用的一些前景。制造智能 MN 贴片所面临的主要挑战是将多个模块（例如药物载体、高灵敏度生物传感器和数据分析器）集成到一个微型 MN 设备中。研究人员已经通过整合刺激响应生物材料和先进的微尺度技术（例如微传感器和微流控系统）来展示了制造智能 MN 的可行性，以精确控制生物流体和药物在整个系统中的输送。这些多功能 MN 设备可以通过两种不同的策略来设想。第一种类型包括具有微流控系统和数字分析仪的单个药物输送和生物传感 MN 单元，负责这些两个模块之间的流体输送和通信。第二种类型依赖于可以通过刺激响应方式释放药物的智能生物材料。当这些智能生物材料暴露于外部刺激（例如 pH 和离子变化）时，它们可以发生结构变化，模拟生物系统。研究表明，水凝胶基 MN 设备在各种生物医学应用中具有很高的潜力，例如药物和细胞输送以及间质液提取。由于具有高载药能力和与所选药物的生物相容性，可生物降解水凝胶在制造多功能 MN 方面也具有优势。在这里，我们首先综述了一组 MN 设备，这些设备可用于生物传感或输送多种靶分子，并将其与主要用于单分子传感或输送的常规和更简单的系统进行比较。随后，我们将我们的见解扩展到具有多种功能的先进 MN 系统，例如在护理点进行体液提取、生物传感和药物输送。生物材料知识和生物制造技术的进步将使我们能够有效地调整下一代智能 MN 并为更有效的个性化治疗提供现实的平台。
